Measurements of concentrations of ammonia, ammonium ion and total ammonia (i.e. the total of the concentrations of ammonia and ammonium ion) are especially useful for the analysis of human blood samples for the diagnosis and treatment of certain metabolic encephalopathies (general deterioration of intellectual function) where blood levels of these become elevated.
For example, elevated blood levels of ammonia, ammonium ion and total ammonia are associated with liver failure from toxins (cirrhosis), infections (hepatitis, Reyes syndrome), hepatic tumors and cardiovascular system dysfunction (congestive heart failure or cor pulmonale). Furthermore, hyperammonia associated with intellectual deterioration can result in epileptics on treatment with valproic acid. Moreover, urinary bladder infections can produce metabolic encephalopathy due to excessive ammonia production by bacteria in the bladder. In the case of liver disease, treatment can involve nutritional treatment as well as administration of cathartics to eliminate ammonia producing bacteria from the bowel. In the valproic acid induced condition, the level of this drug is reduced or eliminated to ameliorate the condition. In the case of bladder infection, the infection is treated e.g. with antibiotics. In all these cases, the measurements as mentioned not only have a diagnostic function but also have a therapeutic function in that they allow determination of whether treatment is effective. Quick and accurate measurements are important because these conditions can lead to coma and death.
Furthermore, the aforementioned measurements can provide indirect but dynamic information about brain neutrotransmitter metabolism of glutamate and aspartate, for example, from direct brain measurements of ammonia/ammonium ion/total ammonia and pH changes.
At physiological pH levels most ammonia exists as ammonium ion (&gt;99%). Thus measurement of ammonium ion concentration is a good estimate of total ammonia content of blood, urine, brain, etc. The best measurement is the sum of ammonium ion concentration and ammonia concentration which is denoted total ammonia both herein and commonly.
Conventionally ammonium ion concentration is measured by an antibiotic based electrode. However, such electrodes do not discriminate between ammonium ion and other monovalent cations sufficiently to allow ammonium ion measurements in biological samples where such interfering ions are present in excess.
Montalvo U.S. Pat. No. 3,869,354 discloses measuring ammonium ion concentration by utilizing a monovalent cationic electrode surrounded with an ammonia permeable but otherwise cation impermeable membrane for selectivity and achieving sensitivity by placing the cation electrode assembly in the test solution and buffering the test solution to the same pH as that of the buffer electrolyte between the covering membrane and electrode.
Strickler et al. U.S. Pat. No. 3,649,505 discloses measuring total ammonia by measuring for ammonia after raising the pH to 11.5 or higher for samples of low total ammonia content.
The methods involving pH adjustment are inconvenient and require buffering or pH adjustment to levels which degrade biological tissues. Furthermore, pH adjustments are not possible when measurements are being made on tissue in vivo.